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| Author(s): |
Liã Bárbara Arruda
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Medicina Tropical de São Paulo (IMT) |
| Defense date: | 2014-06-09 |
| Examining board members: |
Jorge Simão do Rosário Casseb;
Luiz Mario Ramos Janini;
Helder Takashi Imoto Nakaya;
Maria Cecilia Araripe Sucupira
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| Advisor: | Jorge Simão do Rosário Casseb |
| Abstract | |
The tropism of Human Immunodeficiency Virus type 1 (HIV - 1) for CCR5 and CXCR4 coreceptors has provided the development of new therapeutic strategies targeting these coreceptors. CCR5 antagonists are able to prevent the HIV cell entry by blocking the CCR5 coreceptor, improving the viremia decreasing. However, this drug administration depends on viral tropism determination before and during the use of this therapeutic strategy. The V3 loop of the HIV-1 gp120 envelope is the major tropism determinant, but other factors such HIV-1 genetic variability, number of potential N-linked glycosylation sites, length variations in some protein domains and the gp120 global net charge may also affect the viral tropism. This study presents the molecular characterization of gp120 and the relationship between molecular factors and the tropism for CCR5 and CXCR4 coreceptors. A total of 283 HIV-1 infected subjects were included in this study. It was possible to obtain 265 V3 loop sequences, 78 results of phenotypic tropism and 20 sequences of the whole gp120. Phenotypic tropism showed the prevalence of R5 viruses (70.5%) while exclusively X4 viruses were found in only one sample. Genotypic tropism classified 71.7% of the sequences as R5 and 28.2% as virus able to use the CXCR4 correceptor. The agreement between phenotypic and genotypic tropism results was 74.5%. There was a prevalence of subtype B (82%), and the B\' (GWGR) variant was present in 34.5% of the cases. gp120 showed a mean of 22 N-linked glycosylation sites, which were more frequent in the C2 and C4 regions. The net charge showed similar means between R5 and X4 viruses for both V3 loop and gp120. The molecular characteristics described in this study showed similar distribution between R5 and X4 viruses and it was not possible to establish relationships between these factors the tropism determination. (AU) | |
| FAPESP's process: | 10/00222-5 - Molecular characterization of gp120 of HIV-1 and its implications on the coreceptor usage |
| Grantee: | Liã Bárbara Arruda |
| Support Opportunities: | Scholarships in Brazil - Doctorate |